Mayo was carted off in the second quarter of Sunday's victory over the Buffalo Bills after making a tackle on running back Anthony Dixon. It was reported Monday that Mayo was out for the season with a leg injury that is "bad."
Mayo is reportedly hoping his rehabilitation will take six months.
The two-time Pro Bowler missed 10 games last season after tearing a pectoral muscle. Over six games this season, Mayo recorded a team-high 53 tackles.
The Patriots (4-2) host the New York Jets on Sunday.
- Chris Johnson